The study shows that around three out of every 100 women on combined HRT will develop either breast or endometrial cancer over a period of five years. This compares with about two and a half per 100 who take oestrogen-only HRT or tibolone, and around one and a half per 100 who have not taken HRT.

By Cancer Research UK, [RxPG] Some forms of hormone replacement therapy increase the risk of endometrial (womb) cancer, according to results from the Million Women Study, published in the Lancet*(1) today (Friday).

Women taking a relatively new type of HRT, called tibolone*(2), and women taking oestrogen-only HRT are at an increased risk of the disease compared with women who have never taken HRT. Women taking a combination of oestrogen and progesterone have the same or a slightly lower risk of endometrial cancer, compared to women who have never taken HRT.

However, previous research has shown that this combined type of HRT poses a greater breast cancer risk than tibolone or oestrogen-only HRT and, because breast cancer is more common than endometrial cancer, the researchers believe that when considering the overall effect of HRT it is important to look at both breast and endometrial cancer.

When rates for breast and endometrial cancer are taken together, the overall risk is highest in women taking combined HRT.

The study shows that around three out of every 100 women on combined HRT will develop either breast or endometrial cancer over a period of five years. This compares with about two and a half per 100 who take oestrogen-only HRT or tibolone, and around one and a half per 100 who have not taken HRT.

The Million Women Study, funded by Cancer Research UK, the NHS Cancer Screening Programme and the Medical Research Council, includes over a million women aged between 50 and 64 who filled out lifestyle questionnaires, including whether they had taken HRT. Since the late 1990s, when the women were recruited, around 1,300 have developed endometrial cancer and over 10,000 have developed breast cancer.

Lead author Professor Valerie Beral, Director of Cancer Research UK's Epidemiology Unit, explains: "These new results create a dilemma for women who haven't had a hysterectomy and want to use HRT. On one hand, oestrogen-only HRT and tibolone increase the risk of endometrial cancer but, on the other hand, HRT containing both oestrogen and progesterone causes the greatest increase in breast cancer. "Since breast cancer is much more common than endometrial cancer, combined HRT poses the greatest overall cancer risk."

Use of combined and oestrogen-only HRT has fallen over the last three years. Tibolone use has stayed much the same and is now the most common brand of HRT prescribed to women in the study who have not had a hysterectomy*(3).

The study also reinforces the link between obesity*(4) and endometrial cancer; the more overweight a woman is, the greater her risk of endometrial cancer, but this risk varies depending on whether the woman is taking HRT.

Experts believe that oestrogen stimulates growth of the cells in the womb, which can lead to cancer, and women who are obese have higher levels of oestrogen in the blood.

For obese women, oestrogen-only HRT appears to have less impact on the risk of endometrial cancer and this may be because their existing levels of oestrogen are already quite high. Progesterone may go some way towards counteracting the effects of oestrogen, especially in obese women.

Professor John Toy, Cancer Research UK's Medical Director, says: "It's crucial that we understand the effects that drugs can have on our bodies. We already know the impact that HRT has on breast cancer risk and now we understand how it can affect the risk of developing endometrial cancer.

"It's important that women, and the doctors who treat them, are given all the information they need to decide whether to take HRT.

"Our advice remains that women should take HRT for medical need only and the shortest time possible."

*(2) Tibolone, which is sold as Livial®, is a steroid that combines oestrogenic, progestogenic and androgenic activity and has the same licensed indication as conventional HRT. In the late 90s, nine per cent of women in the Million Women Study who had not had a hysterectomy and were using HRT took tibolone. Now the figure is around 15 per cent.

*(3) Because oestrogen-only HRT has already been linked to endometrial cancer, doctors usually only prescribe it to women who have had a hysterectomy. Women who have a womb are usually offered combination HRT or tibolone.

*(4) Someone who has a Body mass index (BMI) of 30 or more is considered obese. BMI is calculated by dividing weight in kilograms by height squared in meters.

* According to the research, an average of 0.6 women out of every 100 who take tibolone developed endometrial cancer over a five-year period. This compares to 0.3 out of every 100 women who had not taken HRT.
* Among women who take oestrogen-only HRT, 0.5 out of every 100 developed endometrial cancer over five years.
* For every 100 women who take combined oestrogen and progesterone, between 0.2 and 0.3 developed endometrial cancer.
* The corresponding figures (per 100 over five years) for breast cancer are 2.0 for tibolone, 1.8 for oestrogen only HRT, 2.8 for combined HRT and 1.4 for women who have never used HRT.
* There are around 5,100 new cases of endometrial cancer diagnosed in the UK each year. For breast cancer, the figure is approximately 41,000.
* Further details of the Million Women Study  specifically the incidence rates for endometrial and breast cancer per 1000 women over five years  can be found at the Million Women Study website: www.millionwomenstudy.org.uk.
* For more information on endometrial cancer, breast cancer and HRT, visit Cancer Research UK's patient information website Cancer Help UK at: www.cancerhelp.org.uk.

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